Impact of Fever and Antipyretic Use on Influenza Vaccine Immune Reponses in Children : The Pediatric Infectious Disease Journal

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Impact of Fever and Antipyretic Use on Influenza Vaccine Immune Reponses in Children

Li-Kim-Moy, Jean MBBS*,†,‡; Wood, Nicholas PhD*,†,‡; Jones, Cheryl PhD§,¶,‖; Macartney, Kristine MD*,†,‡; Booy, Robert MD*,†,‡

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The Pediatric Infectious Disease Journal 37(10):p 971-975, October 2018. | DOI: 10.1097/INF.0000000000001949



Comparing postvaccination fever rates in pediatric influenza vaccine clinical trials is difficult due to variability in how fever is reported. The impact of vaccine-related fever and antipyretic use on trivalent influenza vaccine immunogenicity in children is also unclear.


In this pilot study, we used individual-level data provided by GlaxoSmithKline from 3 pediatric clinical trials of GlaxoSmithKline versus comparator trivalent influenza vaccine. We explored a primary study (NCT00764790), the largest trial involving young children (6–35 months, n = 3317), and further explored key findings in the 2 other trials (3–17 years, NCT00980005; 6 months to 17 years, NCT00383123). We analyzed postvaccination fever and antipyretic use, and their association with immunogenicity through use of multivariable regression.


Postvaccination fever data were reanalyzed from the primary study using the Brighton Collaboration standardized definition (vaccine-related fever ≥38°C, measured by any route, reported after each dose). Rates were substantially lower after first (2.7%–3.4%) and second doses (3.3%–4.1%), than those published (6.2%–6.6%; combined dose data, any causality). A pooled immunogenicity analysis combining the 3 studies (n = 5902) revealed children with postvaccination fever had significantly higher adjusted geometric mean titers than those without fever (ratio, 1.21–1.39; P ≤ 0.01). Conversely those with antipyretic use had significantly lower adjusted geometric mean titers (ratio, 0.80–0.87; P < 0.0006), dependent on virus strain.


Varying analyses and reporting methods can result in substantially different reported fever rates in studies. Standardized reporting of fever is needed to facilitate comparison between studies. Fever and antipyretic use may have important associations with influenza vaccine immunogenicity in children and need further prospective investigation.

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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